Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Immunity. 2011 Mar 25;34(3):396-408. doi: 10.1016/j.immuni.2011.03.005.
TGF-β1 is a regulatory cytokine that has an important role in controlling T cell differentiation. T cell-produced TGF-β1 acts on T cells to promote Th17 cell differentiation and the development of experimental autoimmune encephalomyelitis (EAE). However, the exact TGF-β1-producing T cell subset required for Th17 cell generation and its cellular mechanism of action remain unknown. Here we showed that deletion of the Tgfb1 gene from activated T cells and Treg cells, but not Treg cells alone, abrogated Th17 cell differentiation, resulting in almost complete protection from EAE. Furthermore, differentiation of T cells both in vitro and in vivo demonstrated that TGF-β1 was highly expressed by Th17 cells and acted in a predominantly autocrine manner to maintain Th17 cells in vivo. These findings reveal an essential role for activated T cell-produced TGF-β1 in promoting the differentiation of Th17 cells and controlling inflammatory diseases.
TGF-β1 是一种调节性细胞因子，在控制 T 细胞分化方面具有重要作用。T 细胞产生的 TGF-β1 作用于 T 细胞，促进 Th17 细胞分化和实验性自身免疫性脑脊髓炎（EAE）的发展。然而，对于 Th17 细胞产生所需的确切 TGF-β1 产生 T 细胞亚群及其细胞作用机制仍不清楚。在这里，我们表明，从活化的 T 细胞和 Treg 细胞中删除 Tgfb1 基因，但不是单独删除 Treg 细胞，可阻断 Th17 细胞分化，导致 EAE 几乎完全得到保护。此外，体外和体内的 T 细胞分化表明，TGF-β1 在 Th17 细胞中高度表达，并以主要自分泌的方式在体内维持 Th17 细胞。这些发现揭示了活化的 T 细胞产生的 TGF-β1 在促进 Th17 细胞分化和控制炎症性疾病方面的重要作用。
